Conservation and evolution of gene colexpression networks in human and chimpanzee brains
Conservation and evolution of gene colexpression networks in human and chimpanzee brains
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DOI：
10.1073/pnas.0605938103
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发表时间：
2006-11-21
影响因子：
11.1
通讯作者：
Geschwind, Daniel H.
中科院分区：
文献类型：
--
作者：
Oldham, Michael C.;Horvath, Steve;Geschwind, Daniel H.
人类和非人类灵长类动物大脑之间的基因表达比较已经确定了数百种差异表达的基因，然而将这些列表转化为物种之间的关键功能差异被证明是困难的。在这里，我们通过研究人类和黑猩猩大脑中基因共表达网络的大规模组织，提供了一个更完整的人类大脑进化观点。我们确定了与离散脑区相对应的共表达基因模块，并量化了它们在物种之间的保护。大脑皮层的模块保护明显弱于皮层下大脑区域的模块保护，揭示了与已知进化等级相似的惊人梯度。我们介绍了一种识别物种特异性网络连接的方法，并展示了如何使用差异网络连接来识别进化变化的关键驱动因素。通过将我们的结果与比较基因组序列数据和蛋白质序列分化率的估计相结合，我们确认了许多网络预测并验证了这些发现。我们的结果提供了对灵长类大脑组织的分子基础的见解，并展示了加权基因共表达网络分析的一般效用。
Comparisons of gene expression between human and non-human primate brains have identified hundreds of differentially expressed genes, yet translating these lists into key functional distinctions between species has proved difficult. Here we provide a more integrated view of human brain evolution by examining the large-scale organization of gene coexpression networks in human and chimpanzee brains. We identify modules of coexpressed genes that correspond to discrete brain regions and quantify their conservation between the species. Module conservation in cerebral cortex is significantly weaker than module conservation in subcortical brain regions, revealing a striking gradient that parallels known evolutionary hierarchies. We introduce a method for identifying species-specific network connections and demonstrate how differential network connectivity can be used to identify key drivers of evolutionary change. By integrating our results with comparative genomic sequence data and estimates of protein sequence divergence rates, we confirm a number of network predictions and validate these findings. Our results provide insights into the molecular bases of primate brain organization and demonstrate the general utility of weighted gene coexpression network analysis.